Primates, such as Old World monkeys, represent a crucial research resource, and major scientific advances in medicine, biology, and neuroscience can be attributed to their use. Despite the recent strides made in controlling colony diseases, in developing new housing regimens, and in modernizing facilities, some monkeys develop pathological behavior. Of particular concern is the small but persistent percentage of monkeys that develop the syndrome of self-injurious behavior (SIB). The occurrence of SIB compromises the goal of promoting the physical and psychological well-being of laboratory primates as mandated by the Animal Welfare Act (Revised 1991). It also threatens the quality of the monkey research resource, particularly because monkeys with this condition differ both behaviorally and physiologically from other monkeys in the colony. Our research has shown that monkeys with SIB are more aggressive, are more likely to have experienced early social separation, and have been exposed to more stressful events than normal monkeys. Monkeys with this disorder also show altered heart rate patterns and a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis manifested by unusually low levels of plasma cortisol. This pattern of precipitating stressors and low cortisol parallels similar observations in patients with post-traumatic stress disorder (PTSD). The continuing objective of this project is to characterize the nature of SIB in rhesus monkeys, to identify the mechanisms responsible for this behavioral pathology, and to devise effective treatment regimens. Our current focus is on the HPA and serotonergic systems, both of which may be altered in monkeys with SIB. We will use various endocrine challenges to determine whether monkeys with SIB show reduced adrenocortical responsivity and heightened sensitivity of the glucocorticoid negative feedback system as is observed in PTSD patients. We will determine whether monkeys with SIB show altered stress responses to various social situations using our newly developed procedure of noninvasive collection of salivary cortisol in unrestrained adult animals. We will investigate cardiac and HPA reactions that surround spontaneous episodes of self-directed biting in an effort to determine whether biting serves as a coping strategy to reduce arousal. Other studies will examine the role of the serotonergic system in the expression of SIB by measuring hormonal responses to a fenfluramine challenge. Finally, we will evaluate the efficacy of serotonergic drugs as potential pharmacotherapeutic agents for reducing the incidence of SIB. These studies should provide important new information concerning the pathophysiology of SIB in monkeys and should lead to the development of useful treatment strategies.